Natural and enriched Cr target development for production of Manganese-52

52Mn is a promising PET radiometal with a half-life of 5.6 days and an average positron energy of 242 keV. Typically, chromium of natural isotope abundance is used as a target material to produce this isotope through the nat/52Cr(p,n)52Mn reaction. While natural Cr is a suitable target material, higher purity 52Mn could be produced by transitioning to enriched 52Cr targets to prevent the co-production of long-lived 54Mn (t1/2 = 312 day). Unfortunately, 52Cr targets are not cost-effective without recycling processes in place, therefore, this work aims to explore routes to prepare Cr targets that could be recycled. Natural Cr foils, metal powder pellets, enriched chromium-52 oxide and Cr(III) electroplated targets were investigated in this work. Each of these cyclotron targets were irradiated, and the produced 52Mn was purified, when possible, using a semi-automated system. An improved purification by solid-phase anion exchange from ethanol-HCl mixtures resulted in recoveries of 94.5 ± 2.2% of 52Mn. The most promising target configuration to produce a recyclable target was electroplated Cr(III). This work presents several pathways to optimize enriched Cr targets for the production of high purity 52Mn.

All other materials were purchased from Fisher Scientific (Hampton, NH) unless stated otherwise.
Natural Cr foils. As reported in Pyles et al. 2021, Cr foils were produced on a large scale by electrodeposition of natural abundance Cr as previously described in Wooten et al. 2015 11,13 .
Natural Cr powder targets. Cr metal powder targets were made by pressing 200-230 mg of natural Cr metal powder at 5 tons for 5 min using a hydraulic press and 10 mm dye set. These targets were 10 mm in diameter and had 0.4-0.5 mm nominal thickness. Tantalum (Ta) sheets with 3N8 purity and thickness of 0.06 in, were cut into a 2.5 cm diameter coins and a 0.5 mm deep divot was machined into the center to hold the Cr powder target. Additionally, these targets had a divot for a Viton O-ring outside of the target divot as to prevent the loss of target material. The targets were finally capped with a 0.75 mm Aluminum (Al) degrader with a "push button" design to fit into the 14 mm divot to cover both the target and the O-ring as shown in Fig. 1A.
Enriched Chromium oxide powder targets. 52 Cr 2 O 3 was made by the reactions.   3 . The 52 Cr(OH) 3 was then centrifuged at 3000 rpm for 7 min or until the precipitate was separated from the solution. The precipitate pellet was separated from the supernatant, and rinsed with MQ water. The 52 Cr(OH) 3 was heated at 200-250 °C to obtain the final product of 52 Cr 2 O 3 . Then the 52 Cr 2 O 3 powder was weighed and placed in the oven to keep it dry at 250 °C. The powder targets were made by pressing 200-230 mg of 52 Cr 2 O 3 powder in a 10 mm diameter ID dry pressing die set, to ensure the correct target shape, at 5 tons for 5 min using a hydraulic press to make the pressed pellet used for irradiations. These targets were 10 mm in diameter and had 0.4-0.5 mm nominal thickness. The target was configured as described in Section 1.3 with the Ta backing and Al "push button" degrader as shown in Fig. 1B.
Electroplated Cr(III) targets. Chromium chloride hexahydrate (CrCl 3 ·6H 2 O) was utilized as the chromium source in the electrodeposition solution which was adapted from the procedure previously described in Liang et al. 14 . A 20 × 150 mm lime glass disposable culture tube modified to have two open ends was used as the electrolysis cell. The plating diameter was 10 mm with a 0.1-0.5 mm nominal thickness depending on the amount of Cr plated as shown in Fig. 1C. Copper (Cu) or Gold (Au) sheets with 5N5 and 5N purity, respectively, and thickness of 0.75 mm were cut into a 2.5 cm diameter coins to be used as the target backing (cathode) while a platinum rod was used as the rotating anode suspended in the solution. The electroplating apparatus was connected to a DC power supply that utilized alligator clips in order to apply voltage to the platinum rod. (Fig. 2) The voltage applied to the platinum rod and the electroplating solution was 3.8 V which supplied a current averaging 0.075 A. Additionally, these targets were finally capped with a 0.75 mm Al degrader.
Irradiation parameters. The stopping and range of ions in matter (SRIM) was used to determine the energy of the proton beam on target after the degrader 15 . All bombardments were performed on the TR-24 Cyclotron (Advanced Cyclotron Systems Inc). The irradiations below used bombardment parameters previously optimized by El Sayed et al. These target configurations were irradiated with an incident proton beam energy of 17.5 MeV on the degrader (12.8 MeV on the Cr target material) at 15 μA for 2-8 h. The proton beam was stopped in the backing coin described in each target configuration. The target was cooled by He gas on the front of the target while the back of the target was water cooled.

Target characterization via scanning electron microscope (SEM). The electroplated targets were
analyzed by the SEM to determine the purity of the plated Cr. SEM analysis was performed with a SEM FEI Quanta 650 FEG with secondary electron detector at an acceleration voltage of 16 kV for spectroscopy equipped with an electron dispersive X-ray spectroscopy (EDAX) analyzer to measure qualitatively the sample stoichiometry. The SEM utilized the xT microscope control software while the EDAX used Teams software.
Purification methods. The purification method described below was adapted from Pyles et al. except for the natural Cr foils which used the exact separation process written in Pyles et al. 13 . For the adapted studies, three columns composed of 1 mL solid-phase extraction (SPE) tubes were loaded with AG1-X8 resin as follows: column 1 (C1)-300 mg, column 2 (C2)-200 mg and column 3 (C3)-100 mg. A frit provided with the SPE tubes was added on top of the AG1-X8 resin to prevent the resin bed from being disturbed by the incoming reagents during the purification process. The irradiated Cr target was dissolved in concentrated HCl, diluted to 3% HCl in EtOH and loaded onto a column containing AG1-X8 resin. The Cr was eluted with 3% HCl in ethanol. The Mn was eluted with 6 M HCl.
The adapted procedure of the three-column chemistry separation is described in Table 3 and Fig. 3. Electroplating apparatus used to plate Cr metal from a CrCl 3 solution where the cathode is located between the base plate and the plastic coin holder. The anode is the platinum rod which can be seen connected to the motor and suspended in the CrCl 3 plating solution. Table 3. Chemical separation procedure for the load-wash-elute sequence for a three-column system for the purification of 52 Mn from the cyclotron bombarded Cr targets 13 . Step

Results and discussion
Target preparation and yields. The details of each target configuration's irradiation and purification results are listed in Table 4. The theoretical values for each target were calculated using the thick target yield measurement and are in agreement with the experimental yields.
Natural chromium foils. In the original target configuration of 1-2 natural Cr foil(s) and purification method previously described in Pyles et al., the foils are no longer available and two-three columns were used 13  Unfortunately, this material did not dissolve in any of the following acids and bases in their concentrated forms: hydrochloric acid, nitric acid, sulfuric acid, hydrofluoric acid, and sodium hydroxide. Mixtures of these acids were also attempted without success using aqua regia and piranha solution. This is in line with prior literature reports that harsh conditions are required to dissolve Cr 2 O 3, therefore, this target could not be purified to obtain the purified 52 Mn 16,17 . If a reasonable dissolution was developed these targets could be recycled and reused for an enriched 52 Cr target. The recycling process would utilize the reaction listed to make the 52 Cr 2 O 3 starting with the CrCl 3 that is collected during the purification process.

Electroplated chromium(III).
The electroplated Cr utilizes chromium oxide hexahydrate in the electrodeposition solution. The formic acid and urea were used as complexing agents while the ammonium chloride and sodium chloride were used as conducting salts and finally the methanol and boric acid were used as buffering agents. These targets were further investigated by a scanning electron microscope (SEM) (Fig. 4). The analytical technique confirmed that the electroplated targets contained 95.6 ± 1.0% by weight percent and 89.3 ± 1.1% by atomic percent of Cr on the surface with 3.2 ± 0.2% by weight percent and 9.7 ± 0.6% by atomic percent of oxygen using a Cu backing. The electroplated targets using an Au backing contained 93.5 ± 1.5% by weight percent and 83.1 ± 3.9% by atomic percent of Cr on the surface with 5.6 ± 1.2% by weight percent and 16.5 ± 3.1% by atomic percent of oxygen before sanding the surface and contained 93.7 ± 0.6% by weight percent and 82.0 ± 1.4% by atomic percent of Cr on the surface with 6.3 ± 0.6% by weight percent and 18.0 ± 1.4% by atomic percent of oxygen after sanding the surface. While the amount of Cr is slightly increased on the Cu backing, the Au is more practical as elevated Cu in the final product was observed when the Cu backings were used due to slight dissolution of Cu during the dissolution of the Cr target material. Plating yields were 16.8 ± 2.6% which could be improved for conversion to an enriched recycled target. www.nature.com/scientificreports/ The purification system separated Mn from the Cr target material by using a series of three 1 mL SPE tubes. The results from the radioactive purifications were obtained using the electroplated Cr(III) targets shown in Gamma spectroscopy. The radionuclidic purity of the samples was verified via gamma-ray spectroscopy where samples were acquired before, during and after purification of 52 Mn. 52m Mn (a meta-stable state of 52 Mn with a t 1/2 = 21.1 min) and 50 Mn were not present in the spectra due to their short half-lives. 51 Cr was not present in the spectra where the limit of detection was less than 1.24 ± 0.32%. The amount of 54 Mn detected in the final sample was 0.125 ± 0.124% of the total sample displayed in the top gamma spectra of Fig. 6. When an enriched

Discussion
The Cr target configurations presented explored additional techniques for the possibility of an enriched 52 Cr target that would improve the production of 52 Mn. The novel targets have challenges but could be improved upon with further investigation.
While some Cr foils are commercially available, Cr foils are very difficult to manipulate into discs since the material is brittle. The Cr metal powder was crafted into a pressed pellet for in the production of 52 Mn. While this target configuration works well and could be consistently used for production of 52 Mn it cannot be reused or recycled for a cost-effective means to utilize enriched 52 Cr. 52 Cr could be exchanged for natural Cr in this target configuration to prevent the production of 54 Mn if the cost of the enriched material was not a factor. Ideally, the enriched material would be 100% recycled and the target could be reused multiple times which lead to exploration of additional Cr target configurations.
The Cr 2 O 3 target does have the potential to be recycled since the final Cr species from the purification is CrCl 3 . The CrCl 3 could potentially be reacted to make more Cr 2 O 3 to make a new target. However, we were not able to dissolve this material which leads to purification issues. Finally, the electroplated Cr (III) target is the most promising since it has the potential to be recycled, can be dissolved/purified and it is less toxic than the well-known Cr(VI) electrodeposition. In order to improve the yield of Cr(III) on the Au surface new techniques need to be explored with the aim of yields greater than 90% at a thickness greater than 0.2 mm.
The concentration of the eluting solution affected greatly the AMA of the 52 Mn produced. Higher concentrations of HCl acid selectively released 52 Mn from the resin bed.

Conclusion
Enriched targets for the production of 52 Mn should continue to be investigated in order to obtain a recyclable target that increase the yield and decreases the time of irradiation. Cr foil and Cr metal powder targets are routinely used for the production of 52 Mn, however, these targets cannot be recycled in order to move to the enriched 52 Cr target material. Cr 2 O 3 is not feasible to use for natural or enriched targets because of the dissolution issues. Although the target is capable of giving higher yields when enriched material is used and it is possible to recycle through the CrCl 3 to Cr 2 O 3 reaction, it has been a challenge to dissolve and separate the 52 Mn from the Cr. Finally, the Cr electroplated targets are the most promising for the future of enriched 52 Cr targets for 52 Mn production. These targets have the potential to be recycled by using the final CrCl 3 in the new electroplating solution and the plated Cr can endure more current than the other targets described here leading to increased yields. Top. Representative gamma spectra taken after the 52 Mn purification process of the natural Cr metal powder target (all natural targets discussed showed similar spectra with the same peaks) showing a lack of 51 Cr peak (320.1 keV). However, the 54 Mn peak (835.85 keV), highlighted in red, can still be observed as well as the many characteristic peaks of 52 Mn (345. 8

Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.